Recently we have found that HeLa cells can be induced to undergo morphologic and biosynthetic differentiation by growth in medium with sodium butyrate and certain other aliphatic monocarboxylates. The morphological differentiation consists of the development of specialized intercellular junctions - desmosomes and the organization of microfilaments into tonofilaments which resemble those found in squamous epithelium. These structures are not observed in control cultures and represent an ultrastructural differentiation. Accompanying to morphological differentiation induced by butyrate, the cells synthesize and secrete certain glycopeptide trophic hormones (HCG, FSH, and LH) and show an increase in the activity of the oncofetal isozyme of alkaline phosphatase. The induction by simple chemical compounds of certain specialized structures and functions in cells in culture offers an approach to investigate control of gene expression and perhaps the process of "differentiation". Genetic analysis of cell mutants provides a method for studying the mechanism whereby simple chemical compounds such as butyrate modulate gene expession. Investigation of mutants resistant to the effects of inducers can help in dissecting the essential elements for response in complex cell-inducer interactions. The elucidation of the mechanism of these effects may have relevance for developing methods for the early detection of occult neoplasms by inducing production of tumor marker protein (for example glycopeptide hormones and oncofetal isozymes). Moreover, butyric acid is commonly used as a food presevative and an understanding of its role in modulating gene activity may contribute to our knowledge of carcinogenesis.